Diagnosis and Staging of Typhoid Fever Using Surface-enhanced Raman Spectroscopy Liquid Biopsy

The goal of this project is to adapt the gold nanoparticle-based surface-enhanced Raman spectroscopy (SERS) technology to clinical application. In this exploratory study a measurement protocol will be established to subsequently investigate whether SERS allows to diagnose patients infected with typhoid fever as well as to stage the disease.

This study on the clinical application of surface-enhanced Raman spectroscopy (SERS) is composed of two parts. First, a SERS measurement protocol will be developed to enhance the interactions between gold nanoparticles and the components of the patients samples, maximizing Raman spectroscopical signatures. Given the complex composition of human blood, which encompasses numerous biological constituents, the study focuses on serum, a component obtained through centrifugation after the removal of cells and clotting factors. Fifteen spectra will be recorded per sample. The raw spectra will be post-processed, including removal of the substrate signal, baseline correction, vector normalization, and smoothing steps. The SERS measurement protocol established in the first section will subsequently be applied to samples of healthy and typhoid fever patients. The samples from infected patients will be confirmed with the Widal test. Multivariate data analysis will be performed to identify distinctive feature characteristics in the samples that correlate to their group (healthy and infected patients), allowing patient diagnosis, as well as the severity of the infection.